clinical study of a-319 in the treatment of active/refractory systemic lupus erythematosus

Conditions: Systemic Lupus Erythematosus

Summary: the purpose of the study is to explore the safety and efficacy of recombinant cd19xcd3 double antibody (a-319) in active/refractory systemic lupus erythematosus (sle).

the pathogenic b cells of patients with sle can produce a large amount of autoantibodies, which will form immune complexes and thereby inducing continuously expanding tissue damage and systemic inflammation. a-319 is a kind of recombinant cd19xcd3 double antibody, it can activate internal t cells to target and kill pathogenic b cells. clinical trials of a-319 are currently underway in hematological maliganancies concerning b cell abnormality. preclinical studies have shown the efficacy of a-319 in sle. the aim of this study is to investigate the safety, tolerability, pharmacokinetics (pk), pharmacodynamics (pd), immunogenicity and preliminary efficacy of a-319 in active/refractory sle. patients with active/refractory sle will be invited to participate in the study, to receive a-319 intravenous infusion or subcutaneous injection and follow-up visits of up to 1 years after enrollment.

Eligibility criteria:
inclusion criteria: 1. age 18-60 years old, regardless of gender; 2. participants diagnosed with sle according to the american college of rheumatology (acr) 1997 revised criteria for sle at least 24 weeks prior to signing the informed consent form; 3. active/refractory systemic lupus erythematosus; 4. positive test results for at least one of the following autoantibodies at screening: antinuclear antibodies (ana) immunofluorescence assay at a titer of ≥1:80; anti-dsdna; or anti-smith (anti-sm); 5. receive the standardized and stable treatment for at least 30 days before the first administration of the study drug; 6. female participants tested negative for pregnancy, and participants agreed to use effective contraception throughout the trial; 7. have the ability to understand the nature of the research and voluntarily sign an informed consent form; 8. participants can communicate well with the researchers and complete all visits according to the requirements of the plan. exclusion criteria: 1. severe kidney disease; 2. participants who have central nervous system diseases caused by sle or non-sle disease within 8 weeks before the first administration of the study drug; 3. abnormities of main organ function at screening; 4. medical history that the researchers believe will pose risk to the safety of the participants, or will affect the safety or effectiveness analysis of the study drug; 5. active mycobacterium tuberculosis infection; 6. active hepatitis, or hepatitis b virus surface antigen positive, or hepatitis b virus core antibody positive and hepatitis b virus deoxyribonucleic acid positive, or hepatitis c virus antibody positive at screening; 7. history of human immunodeficiency virus infection, or positive antibodies at screening; 8. positive syphilis spirochete antibody at screening (except false positive caused by sle); 9. participants with chronic active infection or acute infection need systemic anti-infection treatment within 4 weeks before screening, or have superficial skin infection requiring treatment within 1 week before screening; 10. have undergone major surgery or unhealed wounds, ulcers or fractures within 4 weeks before the first administration of the study drug, or plan to perform major surgery during the study period; 11. participants diagonosed with malignant tumors within 5 years before screening; 12. history of important organ transplantation or hematopoietic stem cells/or bone marrow transplantation; 13. have been vaccinated or plan to receive live vaccine or live attenuated vaccine during the research period within 4 weeks before the first administration of the study drug; 14. participated in any clinical trial within 4 weeks before the first administration of the study drug or within 5 half-lives of the study drug of the clinical trial; 15. received targeted drugs (rituximab, jak inhibitors, etc.) at a specific time period before the first administration of the study drug; 16. received intravenous immunoglobulin, prednisone ≥100mg/d or equivalent glucocorticoid therapy within 4 weeks before the first administration of the study drug, or plasma replacement; 17. received il-2, thalidomide, rethidone and traditional chinese medicine within 4 weeks before the first administration of the study drug; 18. known allergies to monoclonal antibody drugs, or allergies to a-319 excipients; 19. participants with depression or suicidal thoughts; 20. women who are pregnant or breastfeeding, or women who plan to be pregnant or breastfeeding during the study period; or men whose sexual partners plan to become pregnant during the study period; 21. any reason that the researchers believe will hinder the subject's participation in the study.

Keywords: systemic lupus erythematosus a-319